Expression and prognostic value of alpha-, beta-, and gamma-catenins indifferentiated thyroid carcinoma.

Abstract

Catenins (alpha, ss, and gamma) are a group of intracellular cell adhesion molecules that unite cytoskeleton with extracellular adhesion system. Abnormal expression of these molecules may have prognostic relevance in various carcinomas, including differentiated thyroid carcinoma (DTC). We have, therefore, evaluated the prognostic value of alpha-, ss-, and gamma-catenins along with traditional risk factors in 206 consecutive DTC patients by immunohistochemistry. Papillary carcinomas showed normal staining pattern for alpha-, ss-, and gamma-catenins in 124 (60%), 136 (67%), and 94 (46%) cases, respectively. Follicular carcinomas expressed alpha-, ss-, and gamma-catenins normally in 16 (48%), 18 (55%), and 8 (32%) cases, respectively. Follicular type of tumor showed more often reduced staining for all catenins than papillary carcinoma (P: = 0.009, P: = 0.004, and P: = 0.002, respectively). Age (>60 yr) and pTNM-stage were related to reduced alpha- and ss-catenin expression levels (P: = 0.027 and P: = 0.026, respectively) and larger size of the tumor to reduced ss- and gamma-catenin expressions (P: = 0.039 and P: = 0.007, respectively). Nodal metastases at the time of primary treatment related to reduced alpha-catenin expression and distal metastases to reduced ss- and gamma-catenin staining signals (P: = 0.022, P: = 0.014, and P: = 0.039, respectively). Reduced alpha-catenin associated with tumor recurrence (P: = 0.002) and reduced ss-catenin with cancer-related mortality (P: = 0.005). The multivariate analysis for recurrence-free survival showed that alpha-catenin and serum thyroglobulin level 1 yr after primary treatment were prognostic of recurrent disease (hazards ratio, 3.42, P: = 0.022; and hazards ratio, 10.03, P: = 0.0001). In addition, alpha-catenin retained its prognostic significance in low-stage patients (P: = 0.0151). We propose that the evaluation of alpha-catenin expression by immunohistochemistry in DTC patients has prognostic value in addition to that obtained by traditional prognostic factors.